NIMH-funded study examines whether switching to a different antipsychotic can reduce side effects while maintaining effectiveness

July 22, 2011 • Science Update

Patients experiencing cardiovascular or metabolic side effects while taking an antipsychotic medication may fare better if they switch to a different medication provided they are closely monitored, according to an NIMH-funded study. The study was published online ahead of print July 18, 2011, in the American Journal of Psychiatry.

Antipsychotic medications can effectively treat psychotic symptoms among people with schizophrenia or related disorders. However, the medications, especially some of those that are most commonly used, are associated with serious metabolic side effects that can lead to heart disease or diabetes. Even when patients do experience these side effects, doctors are often reluctant to change a patient’s medication regimen if the patient’s psychotic symptoms are controlled by the existing medication.

“Treating the symptoms of schizophrenia is a delicate balancing act between risks and benefits,” said National Institute of Mental Health Director Thomas R. Insel, M.D. “The possible benefits of switching medications to reduce metabolic risks must be carefully weighed against the potential risk of symptom relapse or medication failure.”

Scott Stroup, M.D., of Columbia University and colleagues aimed to determine if a medication switch could be made safely and without sacrificing clinical stability. For the Comparison of Antipsychotics for Metabolic Problems (CAMP) study, they enrolled 215 patients from 27 clinical sites whose psychotic symptoms were stabilized on one of three frequently used antipsychotics (olanzapine, quetiapine or risperidone) but were experiencing serious metabolic side effects such as weight gain and high cholesterol levels. Half of the patients were assigned to stay on their current medication, while the other half were switched to aripiprazole, another antipsychotic that is generally associated with fewer metabolic risks. All of the participants received a behavioral intervention that included a diet and exercise program designed to reduce the risk of cardiovascular disease.

After 24 weeks, the researchers found that those who switched to aripiprazole had improved cholesterol levels and other metabolic factors, and lost more weight (average of 8 lbs) than those who stayed on their original medication (average of 1.5 lbs). Those who switched also did not experience any more illness relapses or worsening of psychotic symptoms compared to those who stayed on their original medication. However, those who switched to aripiprazole were more likely to discontinue the new medication compared to those who stayed on their original medication. Almost 44 percent of those who switched discontinued the aripiprazole compared to 24.5 percent of those who were assigned to stay on their current medication.

The authors suggest that the high discontinuation rate for switchers may have been related to the fact that the study was open label, meaning both the patient and the clinician knew what drug the patient was taking. Some patients who were switched may have felt uncomfortable changing from a medication they knew worked for them, and therefore stopped the new medication. In addition, because clinicians were encouraged to closely monitor and intervene before a patient experienced severe problems, many may have discontinued aripiprazole when the clinician first determined that the patient was having difficulties, but before full-blown treatment failure occurred.

“For patients whose symptoms are stabilized but who are overweight or experiencing other metabolic problems, clinicians may want to consider switching to a medication that is less likely to cause metabolic problems. However, because switching is not always successful, clinicians must monitor patients carefully to avoid illness exacerbation,” said Dr. Stroup. “If switching medications is not an option, then adding a medication like metformin or a statin could help reduce cardiovascular risks while maintaining symptom stability,” he concluded. He also noted that the study’s behavioral intervention that focused on improved diet and exercise habits benefited even those who did not switch medications.